U.S. patent number 6,890,076 [Application Number 10/231,491] was granted by the patent office on 2005-05-10 for method and apparatus for using adaptive optics in a scanning laser ophthalmoscope.
This patent grant is currently assigned to University of Houston, University of Rochester. Invention is credited to Austin Roorda.
United States Patent |
6,890,076 |
Roorda |
May 10, 2005 |
Method and apparatus for using adaptive optics in a scanning laser
ophthalmoscope
Abstract
A scanning laser ophthalmoscope incorporates adaptive optics to
compensate for wavefront aberrations in the eye. Light from a light
source is scanned onto the retina. Light reflected from the retina
is detected for imaging and is also used for wavefront sensing. The
sensed wavefront aberrations are used to control an adaptive optic
device, such as a deformable mirror, disposed in the path of the
light from the source in order to compensate for the
aberrations.
Inventors: |
Roorda; Austin (Houston,
TX) |
Assignee: |
University of Rochester
(Rochester, NY)
University of Houston (Houston, TX)
|
Family
ID: |
23227824 |
Appl.
No.: |
10/231,491 |
Filed: |
August 30, 2002 |
Current U.S.
Class: |
351/205; 351/221;
351/246; 359/202.1 |
Current CPC
Class: |
G01J
9/00 (20130101); G02B 26/06 (20130101); A61B
3/1025 (20130101) |
Current International
Class: |
A61B
3/12 (20060101); A61B 3/113 (20060101); A51B
003/00 (); A51B 003/10 (); G02B 028/08 () |
Field of
Search: |
;351/200,205,206,211-216,220,221,246,247 ;348/195,202,203,205
;359/196,197,201,202,298 ;600/558 ;128/898 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
Other References
Austin Roorda et al, "Adaptive optics scanning laser
ophthalmoscopy," Optics Express, vol. 10, No. 9, May 6, 2002, pp.
405-412. .
Austin Roorda et al, "Adaptive optics scanning laser
ophthalmoscopy," Optics Express, vol. 10, No. 9, May 6, 2002, pp.
405-412..
|
Primary Examiner: Casler; Brian L.
Assistant Examiner: Sanders; John R.
Attorney, Agent or Firm: Blank Rome LLP
Government Interests
STATEMENT OF GOVERNMENT INTEREST
The present invention was developed under NIH Grant No. R1 EY
13299-01 and NSF Grant No. AST 9876783. The government has certain
rights in the invention.
Parent Case Text
REFERENCE TO RELATED APPLICATION
The present application claims the benefit of U.S. Provisional
Application No. 60/316,173, filed Aug. 30, 2001, whose disclosure
is hereby incorporated by reference in its entirety into the
present disclosure.
Claims
What is claimed is:
1. A method of imaging an area of a retina of a living eye, the
method comprising: (a) providing light from a light source; (b)
injecting the light from the light source into a common optical
path; (c) performing a two-dimensional transverse scan of a focused
spot of the light from the light source on the area of the retina;
(d) receiving light reflected from the focused spot on the retina
back into the common optical path; (e) from a first portion of the
light reflected from the retina, detecting a wavefront aberration
of the eye; (f) disposing an adaptive optical element in the common
optical path between the light source and the eye; (g) controlling
the adaptive optical element to compensate for the wavefront
aberration in the light scanned on the area of the retina to
project the focused spot onto the retina; (h) controlling the
adaptive optical element to compensate for the wavefront aberration
in the light reflected from the focused spot on the retina back
into the common optical path; and (i) from a second portion of the
light reflected from the retina, producing an image of the area of
the retina.
2. The method of claim 1, wherein step (d) comprises descanning the
light reflected from the retina.
3. The method of claim 1, wherein the adaptive optical element
comprises a deformable mirror.
4. The method of claim 1, wherein step (c) comprises raster
scanning a light spot on the retina.
5. The method of claim 4, wherein the raster scanning is performed
with at least one scanning mirror.
6. The method of claim 5, wherein step (c) further comprises
controlling a sweep angle of the at least one scanning mirror to
control a size of an area on the retina which is scanned.
7. The method of claim 1, wherein step (e) is performed with a
Hartmann-Shack detector.
8. The method of claim 7, wherein: step (i) is performed with a
photodetector; and the method further comprises providing a beam
splitter in the common optical path to split the light reflected
from the retina between the Hartmann-Shack detector and the
photodetector.
9. The method of claim 8, wherein the beam splitter comprises a
rotating mirror having mirrored segments and transparent segments
for time division of the light reflected from the retina.
10. The method of claim 9, wherein a period of the time division
equals a period of the scanning of step (c).
11. The method of claim 1, wherein steps (e) and (g) are performed
iteratively.
12. The method of claim 1, wherein steps (e) and (i) are performed
concurrently.
13. The method of claim 1, further comprising (j) controlling the
adaptive optical element for axial sectioning.
14. The method of claim 13, wherein step (g) comprises correcting
the focus to a non-null state.
15. The method of claim 13, wherein step (i) comprises producing a
three-dimensional image of the retina.
16. The method of claim 1, further comprising using the image to
diagnose a disorder of the retina.
17. The method of claim 1, further comprising using the image to
track movement of the eye.
18. The method of claim 1, wherein step (c) comprises projecting a
stimulus or treatment to the retina.
19. The method of claim 1, wherein step (i) is performed a
plurality of times to form a sequence of said images, and further
comprising using the sequence of said images to measure a flow of
blood cells in at least one capillary of the retina.
20. The method of claim 1, wherein step (i) is performed with a
confocal pinhole and a photodetector.
21. A system for imaging an area of a retina of a living eye, the
system comprising: a light delivery section, comprising a light
source, for providing light from the light source and for injecting
the light from the light source into a common optical path; a
scanning section for performing a transverse two-dimensional scan
of a focused soot of the light from the light source on the area of
the retina such that light reflected from the focused spot on the
retina is received back into the common optical path; a wavefront
sensing section, receiving a first portion of the light reflected
from the retina, for detecting a wavefront aberration of the eye; a
wavefront compensation section, comprising an adaptive optical
element disposed in the common optical path between the light
source and the eye, for compensating for the wavefront aberration
in the light scanned on the area of the retina to project the
focused spot onto the retina and for compensating for the wavefront
aberration in the light reflected from the focused spot on the
retina back into the common optical path; and a light detection
section, receiving a second portion of the light reflected from the
retina, for producing an image of the area of the retina.
22. The system of claim 21, wherein the scanning section descans
the light reflected from the retina.
23. The system of claim 21, wherein the adaptive optical element
comprises a deformable mirror.
24. The system of claim 21, wherein the scanning section comprises
a device for raster scanning a light spot on the retina.
25. The system of claim 24, wherein the device for raster scanning
comprises at least one scanning mirror.
26. The system of claim 21, wherein the wavefront sensing section
comprises a Hartmann-Shack detector.
27. The system of claim 26, wherein; the light detection section
comprises a photodetector; and the system further comprises a beam
splitter in the common optical path for splitting the light
reflected from the retina between the Hartmann-Shack detector and
the photodetector.
28. The system of claim 27, wherein the beam splitter comprises a
rotating mirror having mirrored segments and transparent segments
for time division of the light reflected from the retina.
29. The system of claim 21, wherein the light detection section
comprises a confocal pinhole.
30. The method of claim 14, wherein steps (e) and (g) are performed
iteratively to correct the focus to the non-null state.
Description
FIELD OF THE INVENTION
The present invention is directed to scanning laser ophthalmoscopes
(SLO) and methods of using them, and more particularly to such
ophthalmoscopes and methods of using them which involve the use of
adaptive optics (AO) to compensate for wavefront aberrations in the
eye under examination.
DESCRIPTION OF RELATED ART
The development of ocular imaging has progressed since the first
scanning laser ophthalmoscope (SLO) was disclosed in U.S. Pat. No.
4,213,678. The first patent relating to imaging the ocular fundus
while correcting for eye aberrations was Bille's patent titled,
"Method and Apparatus for forming an image of the ocular fundus"
(U.S. Pat. No. 4,579,430). A scanning laser ophthalmoscope for high
lateral-resolution imaging was developed which was capable of
imaging a living human eye but did not use adaptive optics (AO) and
had limited resolution at the microscopic level.
The first published report of using AO in a SLO was by Dreher et
al, "Active optical depth resolution improvement of the laser
tomographic scanner," App. Opt. 28, 804-808 (1989), to improve the
axial resolution of their instrument. The authors of that article
did not use a wavefront sensor to measure the aberrations of the
eye, and their wavefront corrector was used only to compensate for
the astigmatism of the eye. Similarly, the axial resolution of a
SLO has been improved by using a rigid contact lens to eliminate
the aberrations of the cornea, and modest improvements in a fundus
image has been obtained with a fundus camera equipped with a
membrane deformable mirror. Liang et al, "Supernormal vision and
high-resolution retinal imaging through adaptive optics," J. Opt.
Soc. Am. A 14, 2884-2892 (1997), used an ophthalmoscope equipped
with AO to image microscopic structures in the retina, but they did
not apply the technology to a SLO.
In U.S. Pat. No. 6,095,651, a Hartmann-Shack wavefront sensor and
wavefront compensation device are used to measure the high-order
aberrations of the eye. A Hartmann-Shack wavefront sensor was also
used by Bille in U.S. Pat. No. 6,155,684 to measure aberrations for
wavefront compensation as a means to improve vision. A modified
Hartmann-Shack wavefront sensor is described by Williams et al. in
U.S. Pat. No. 6,199,986, wherein a method for real time measurement
of the aberrations of the eye is described.
Therapeutic applications of SLOs with AO include
microphotocoagulation and photodynamic therapy. In U.S. Pat. No.
6,186,628, Van de Velde describes the use of a scanning laser
ophthalmoscope with an adaptive element for microphotocoagulation
and photodynamic therapy. The wavefront sensing technique,
described in another patent, entitled "Scanning laser
ophthalmoscope for retinal microphotocoagulation and measurement of
wavefront aberrations" (U.S. Pat. No. 5,943,117) employs a SLO to
measure the wavefront aberrations of the eye. This technique is not
used widely.
Although there are a number of patents covering SLO's, they do not
propose a method for wavefront sensing whereby the light path is
scanned/descanned using the same optics and light source as that
used for imaging the ocular fundus. Methods that do not use the
same optics for wavefront sensing and light detection are subject
to a common phenomena called "non-common path errors," where the
aberrations on the path to the wavefront sensor are different than
those reaching the light detector for imaging.
By implementing AO to measure and correct high-order aberrations in
an areal imaging system, such as a CCD camera or a film camera, the
quality of retinal images will be improved. However, areal imaging
techniques are limited in that they cannot suppress light from
layers in front of or behind the focal plane of the ophthalmoscope.
Because of this limitation, the images may have high resolution,
but will suffer from low contrast because of scattered light from
structures outside of the best focal plane.
To date, there has been no successful application of AO into a SLO.
The one previous design published by Dreher et al. did not include
wavefront sensing in the measurement. The benefits of AO cannot be
realized without wavefront sensing being an integral part of the
system. Bille's above-cited patent describes a design for a SLO
that integrates a wavefront sensor into the design, but it does not
use the same path as the light detection path and is therefore
subject to the problem of non-common path errors.
SUMMARY OF THE INVENTION
It will be apparent from the above that a need exists in the art to
integrate adaptive optics into retinal imaging. It is therefore an
object of the invention to provide a scanning laser ophthalmoscope
with adaptive optics.
It is another object of the invention to do so while avoiding
non-common path errors.
It is a further object of the invention to provide axial sectioning
in a scanning laser ophthalmoscope.
To achieve the above and other objects, the present invention is
directed to a system and method whereby AO can be efficiently and
effectively implemented in a scanning laser ophthalmoscope. The
present invention will be an improvement on instruments used to
take microscopic images of the retina in living human eyes and will
have improved optical sectioning capability over currently
available SLO's.
The present invention's implementation of AO is efficient because
it uses the same optical path as the SLO. The present invention's
implementation is effective because it is designed to optimize
image quality, both axially and laterally, over the entire field of
view of the ophthalmoscope.
The SLO is a device used to take images of the retina of a living
human eye. In the SLO, scattered light is measured from a focused
spot of light as it is scanned across the retina in a raster
pattern. The image is built over time, pixel by pixel, as the spot
moves across the retina. An aperture conjugate to (in the image
plane of) the desired focal plane in the retina and prior to the
light detector can be used to reduce scattered light originating
from planes other than the plane of focus. The confocal aperture
can be used to do optical slicing, or imaging of different layers
in the human retina.
AO describes a set of techniques to measure and compensate for
aberrations, or optical defects, in optical systems. AO, when
applied to the optical system of the eye, can provide substantial
improvements in the sharpness of retinal images that are normally
degraded from the aberrations. Implementation of AO requires the
use of a wavefront sensor, which is a device to measure the
aberrations of the optical system, and a wavefront corrector, which
is a device used to compensate for the aberrations in an optical
system.
In one particular embodiment, the adaptive optics scanning laser
ophthalmoscope (AOSLO) can be broken down into five main
components: light delivery, light detection, wavefront sensing,
wavefront compensation and raster scanning.
(i) Light delivery: Light delivery can be from a plurality of laser
sources of different wavelengths, depending on the application.
Light is relayed through the instrument via mirrors, which do not
suffer from chromatic aberration. Furthermore, unlike lenses,
mirrors do not produce back reflections that can enter into the
light detection arm.
(ii) Light detection: Light is detected with a detector such as a
very sensitive light detector and amplifier; in a preferred
embodiment, a photomultiplier tube is used. Prior to the light
detector in the preferred embodiment is the confocal pinhole, which
is placed conjugate to the focal plane of the system. The confocal
pinhole is used to limit light reaching the detector to that
originating from the plane of focus.
(iii) Wavefront sensing: Wavefront sensing takes place in the
detection arm of the instrument. The wavefront sensor measures the
optical defects of the eye in the plane of the entrance pupil.
(iv) Wavefront compensation: Wavefront compensation is done with
adaptive optics such as a deformable mirror. The shape of the
deformable mirror is set to exactly compensate the distortions in
the light that are caused by the aberrations of the eye.
(v) Raster scanning: Raster scanning is used to move the focused
spot across the retina in a raster pattern. The extent of the
pattern defines the area of the retina that is being imaged.
Positional outputs from the scanning mirrors, combined with
scattered intensity information from the light detector, are used
to reconstruct the retinal image. Setting the sweep angle on the
scanning mirrors controls the field size of the image.
During operation of the embodiment just described, light is being
scanned in a raster pattern across the retina. The input light beam
is stationary from light delivery through the deformable mirror and
up to the first scanning mirror. The horizontal scanning mirror
adds a horizontal sweeping motion to the beam. The second scanning
mirror adds a vertical sweep to the beam. Both sweeping motions are
done in planes that are optically conjugate to the pupil of the eye
so that the beam at the plane of the pupil is stationary but it
still makes a raster pattern on the retina. This property is
accomplished by using relay optics between each beam-altering
element in the system. According to the law of reversibility of
light, the scattered light from the focused spot on the retina
returns along the same path that the light traveled to generate the
spot. In other words, the scattered light follows the scanning beam
but in the opposite direction. The scattered light also gets
descanned after passing through the same raster scanning mirrors.
By the time the returning light has passed the horizontal scanning
mirror, the beam is again stationary. Aberrations in the scattered
light are compensated by the deformable mirror and are bounced off
a beam splitter into the light detection and wavefront sensing path
of the AOSLO. Having a stationary beam in the light detection arm
allows the scattered light to be focused through a fixed confocal
pinhole, which gives the SLO its optical sectioning capability.
Light is scanned over the retina in a raster pattern while the beam
remains stationary in the plane of the pupil. After scattering, the
optics of the SLO descan the beam and image the pupil of the eye
onto the lenslet array of the Hartmann-Shack wavefront sensor, or
the corresponding element of another wavefront sensor, e.g., a
scanning wavefront sensor. The pupil is conjugate to the lenslet
array, which means that the aberrations are measured in the pupil
plane of the eye. The focused spots in the Hartmann-Shack wavefront
sensor image are also stationary because the beam has been
descanned. An image of the focused spot array in the Hartmann-Shack
sensor is obtained by taking a time exposure of the focused spots
with a CCD array detector. These spot images are analyzed to
determine the aberrations of the eye being measured. In a typical
Hartmann-Shack wavefront measurement, the aberrations are measured
for light originating from a stationary focused spot on the retina.
In high-speed ophthalmic Hartmann-Shack applications, a system that
employs a linear scanning spot has been developed. In this
implementation, the source of the light on the retina is constantly
moving in a raster during the time exposure, and the Hartmann-Shack
sensor measures the average wavefront aberration over the entire
field of the image. The aberration over the image field is expected
to change slightly because aberrations change with off-axis object
position. Nonetheless, these changes are small since it has been
demonstrated that the eye is nearly isoplanatic over a one-degree
field. Therefore, the use of a scanning beam as the source does not
present a disadvantage to the measurement, but rather it presents
several unique advantages, which are listed below:
1) By using the same light source for wavefront sensing and
imaging, the optics are simplified (no additional light source is
necessary for wavefront sensing), and no correction has to be made
for the chromatic aberration of the eye between the wavefront
sensing and imaging wavelengths.
2) Wavefront sensing is always done on the same retinal region as
the images that are taken, since the source of the wavefront
measurement is also the imaging light.
3) Measuring and compensating the average wavefront over the entire
image field will result in a more uniform correction for
aberrations, which will result in better image quality over the
field.
4) Wavefront measurements are not affected by noise due to laser
speckle since the time-averaged image of a moving spot on the
retina despeckles the image. This advantage has already been
applied to wavefront sensing but not to its application for
SLO.
5) The wavefront-sensing configuration described here is easily
adaptable to real-time wavefront sensing and compensation. This
advantage stems from the fact that the wavefront sensing signal is
always present during imaging since imaging and wavefront sensing
use the same light source.
6) The optical path to the wavefront sensor is the same as to the
photomultiplier, with the exception of three aberration-corrected
achromatic lenses (two in the wavefront sensor path and one in the
photomultiplier path). The aberrations that are measured in the
wavefront sensor will be the same as the aberrations of the light
reaching the confocal pinhole, which reduces the non-common path
errors.
In at least one embodiment, the wavefront compensation is done with
a deformable mirror (DM) placed conjugate to the pupil in the
stationary part of the optical path, prior to the raster scanning
mirrors. Having the DM in this part of the path means that the
mirrors that are used to focus the pupil image onto the DM can be
as small as the maximum beam diameter and do not have to be
enlarged to enclose the maximum scan angle. This reduces the size
and cost of the instrument and maintains better image quality in
the optics of the instrument.
By using AO in a SLO, the lateral resolution of retinal images is
expected to improve by up to three times. This has already been
demonstrated in conventional ophthalmoscopes equipped with AO. The
main advantage of applying AO in a SLO will be the improvements in
axial resolution. The axial resolution may be improved by up to 10
times over conventional SLO's.
Equivalent Technologies: Successful implementation of AO in a SLO
does not rely on the specific technologies described in this
disclosure. The following two paragraphs describe equivalent AO
technologies that can be implemented with the same advantages.
Any wavefront sensing technology can be employed that is based on
objective measurement and does not rely on coherent light to
perform the wavefront measurement. Alternative techniques include
but are not limited to laser ray tracing techniques, Tscherning
aberroscopic techniques and crossed-cylinder aberrometer
techniques.
Any wavefront compensation technique can be employed that does not
rely on the use of coherent light. Alternative methods for
wavefront sensing include, but are not limited to, liquid crystal
spatial light modulators, micro-electro-machined (MEMs) membrane
mirrors, MEMs segmented mirrors, bimorph deformable mirrors and
electrostatic membrane deformable mirrors.
One set of applications involves the direct imaging applications
that will benefit from high-resolution images. Such applications
include the early diagnosis of retinal disorders like diabetic
retinopathy, retinitis pigmentosa, age-related macular
degeneration, or glaucoma. Other applications will be to visualize
structures in the retina such as the nerve fibers, cone and rod
photoreceptors, single capillaries in the retina and choroid, and
retinal pigmented epithelium cells. High-resolution imaging will
help retinal surgeons maintain a sharper image of the retina during
retinal surgery.
Another set of applications are those whereby the SLO is used to
image the retina at 30 frames per second and is used to observe
directly the flow of single white blood cells.
Another set of applications are those where stimuli or treatment
lasers are projected directly onto the retina as part of the raster
scan. These applications include photodynamic therapy, laser
microphotocoagulation, microperimetry of the retina, and eye
tracking.
The SLO can use a confocal pinhole to suppress light from outside
of the focal plane, which gives the SLO its optical slicing
capability. This property of the SLO can be improved by
implementing AO to measure and correct the aberrations of the eye.
By reducing the aberrations of the eye through AO compensation,
both axial and lateral resolution can be improved.
BRIEF DESCRIPTION OF THE DRAWINGS
A preferred embodiment of the present invention and variations
thereof will be disclosed in detail with reference to the drawings,
in which:
FIG. 1 is a schematic diagram of a scanning laser ophthalmoscope
incorporating adaptive optics;
FIG. 2 is a flow chart of operational steps carried out with the
ophthalmoscope of FIG. 1;
FIG. 3 is a graph of detected wavefront aberrations for multiple
iterations of wavefront sensing and compensation;
FIG. 4 is a graph of a horizontal angular position of a scanning
line on the retina;
FIGS. 5A and 5B are schematic diagrams of a time-share beam
splitter usable in the ophthalmoscope of FIG. 1;
FIGS. 6A and 6B show images of a retina taken without and with
aberration correction, respectively;
FIGS. 7A-7C show images taken of different axial sections of a
retina;
FIG. 8 shows a video image sequence in which a blood cell is moving
through a retinal capillary; and
FIG. 9 shows images of cone cells taken at various locations on a
retina and calculations of their spacing.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
A preferred embodiment of the present invention and variations
thereof will now be set forth in detail with reference to the
drawings, in which like reference numerals refer to like elements
or operational steps throughout.
FIG. 1 shows a schematic diagram of the scanning laser
ophthalmoscope using adaptive optics (AOSLO). In FIG. 1, points on
the optical path which are conjugate to the pupil of the eye are
labeled p, while points on the path that are conjugate to the
retina are labeled r.
As mentioned above, the AOSLO 100 includes a light delivery section
102, a light detection section 104, a wavefront sensing section
106, a wavefront compensation section 108 and a raster scanning
section 110. All five sections are under the control of a computer
112.
In the light delivery section 102, light from a fiber optic light
source 114 is expanded by a beam expander 116 and collimated by a
collimating lens 118. The collimated light is made incident on an
artificial pupil 120 to produce a smaller beam of light, which is
injected into the common optical path O of the AOSLO 100 by a 5%
reflecting beam splitter 122.
Once in the optical path O, the light is reflected by spherical
mirrors 124 and 126 to the wavefront compensation section 108.
Mirrors are used both to fold the optical path, thereby making the
system more compact, and to avoid the problems of chromatic
aberration and back reflection that affect lenses. The wavefront
compensation section 108 includes a deformable mirror 128. As known
in the art, the deformable mirror 128 includes a deformable mirror
surface 130 deformed by multiple actuators (e.g., piezoelectric
actuators) 132. An example of a deformable mirror is the 37-channel
deformable mirror produced by Xinetics, Andover, Mass. The
deformable mirror 128 is placed in the common optical path O
conjugate to the entrance pupil of the eye E. Under the control of
the computer 112, the actuators 132 deform the mirror surface 130
to compensate for wavefront aberrations in a manner that will be
described in detail below.
Light reflected from the mirror surface 132 is reflected to a
spherical mirror 134 and thence to the raster scanning section 110.
In the raster scanning section 110, the light is reflected via a
spherical mirror 136 to a horizontal scanning mirror 138, which is
implemented as a resonant scanner under control of the computer
112. The light horizontally scanned by the horizontal scanning
mirror 138 is reflected via two spherical mirrors 140 and 142 to a
vertical scanning mirror 144, which is implemented as a
galvanometric scanner under control of the computer 112. A resonant
scanner-galvanometric scanner combination produced by
Electro-Optics Products Corp., Flushing Meadows, N.Y., can be used.
The light which has been both horizontally and vertically scanned
is reflected via spherical mirrors 146 and 148 to the retina of the
eye E. The light is scanned across an area of the retina whose
extent is determined by the horizontal and vertical scanning
extents of the scanning mirrors 138 and 144, which in turn are
controlled by the computer 112.
Light reflected from the retina of the eye E travels back along the
common optical path O, in which it is descanned by the scanning
mirrors 144 and 138, to a beam splitter 150 to be split between the
light detection section 104 and the wavefront sensing section 106.
The beam splitter 150 can be implemented as a partially reflecting
mirror, although an active beam splitter will be described in
detail below.
The portion of the light diverted to the light detection section
104 is focused by a lens 152 onto a confocal pinhole 154 which is
in a plane conjugate to the retina. Light passing through the
confocal pinhole 154 is imaged by a photomultiplier tube 156 to
produce signals which can be converted into an image by the
computer 112. The hardware used can be a GaAs photomultiplier tube
from Hamamatsu, Japan, and a GenesisLC frame grabbing board from
Matrox, Montreal, Quebec, Canada.
The portion of the light passed to the wavefront sensing section
106 is collimated by lenses 158 and 160 and is passed to a
Hartmann-Shack detector 162. As known in the art, the
Hartmann-Shack detector 162 includes a lenslet array 164 which
breaks up the light into an array of spots and a CCD camera or
other suitable imaging device 166 which images the spots. The
deviation of each spot from the position which it would occupy in
the absence of wavefront aberrations allows a determination of
those aberrations in the computer 112. Techniques for determining
the aberrations up to the tenth Zernike order are known in the art.
The computer 112 uses those aberrations to control the deformable
mirror 128 to compensate for those aberrations.
A drawback of using mirrors is that astigmatism and other
aberrations are introduced when they are off axis. To overcome that
drawback, a cylindrical correction can be placed in the spectacle
plane of the eye, and optical design software such as ZEMAX,
published by Focus Software, Tucson, Ariz., can be used to minimize
the remaining high-order system aberrations through optimal
placement of the mirrors. Off-the-shelf spherical reflecting
mirrors can be used.
The AOSLO 100 operates as shown in the flow chart of FIG. 2. In
step 202, the light delivery section 102 injects light into the
common optical path O. In step 204, the scanning section 110 scans
the retina. In an optional step 206, the retina can be axially
scanned, in a manner to be described below, to produce a
three-dimensional image.
In step 208, the wavefront sensing section 106 senses the wavefront
aberrations. In step 210, the wavefront compensation section 108
compensates for those aberrations. Steps 208 and 210 can be
performed iteratively.
In step 212, the light detection section 104 images the retina. In
step 214, the image of the retina is used for any desired purpose,
including diagnosis of the retinal condition, surgery on the
retina, application of therapeutic laser light to the retina, or
eye movement tracking, as will be explained in detail below.
As just noted, the steps of sensing and compensating the wavefront
aberrations can be performed iteratively. FIG. 3 shows the results
of such iterations for a 6.3 mm pupil in a living human eye. The
x-axis is the time in seconds over which the correction took place.
Each point represents the root mean square aberration after a
single iteration. The magnitude of aberrations, measured up to the
tenth order in this case, is reduced sixfold for the 6.3 mm
pupil.
A specific embodiment of the beam splitter 150 and its operation,
namely, the timeshare embodiment, will be described. FIG. 4 shows a
graph of the horizontal angular position of the horizontally
scanned line on the retina as a function of time. As shown, the
position is a sinusoidal function of time, which has roughly linear
sections. During the linear section of each forward scan F, the
scattered light is detected by the light detection section 104 to
image one line in a frame in which the retina is imaged. During the
linear section of each reverse scan R, the scattered light is
passed to the wavefront sensing section 106 to measure the
wavefront aberration.
The structure of the beam splitter 150 is shown in FIGS. 5A and 5B.
The beam splitter 150 includes a disk 502 rotated by a motor 504.
The disk 502 has mirrored segments 506 alternating with
non-mirrored segments 508, so that the light is alternately
reflected to the light detection section 104 and passed to the
wavefront sensing section 106.
The reverse direction R of the scan can be used for wavefront
sensing by splitting the light between the wavefront sensor and the
photomultiplier tube with the segmented mirror that alternates
between transmitting the light to the wavefront sensor and
reflecting the beam toward the photomultiplier tube. The timing of
the mirror is phase-locked to the horizontal scan frequency. The
light reaching the wavefront sensor can be integrated for any
desired period of time independently of the scan rate or the frame
rate of a typical AOSLO. The aberrations of the eye change
dynamically and so the image quality will be better if the eye's
aberrations are measured and compensated while the retina is
imaged.
The deformable mirror can be used as an axial scanning element in
axial sectioning. Axial sectioning requires an optical correction
to change the depth plane of the focused raster scan on the retina.
The use of the deformable mirror presents some unique advantages,
which include reducing the number of moving parts in the system,
and increasing its speed and precision. The thickness of the retina
is about 300 microns. A focal change of less than 1 diopter is
sufficient to change the focal plane by this amount.
The present method can be implemented with the deformable mirror
described in the current design or it can be done with alternate,
dynamic wavefront compensation techniques, such as micro-electrical
machined (MEMs) deformable mirrors, or membrane mirrors.
Wavefront sensing and correction can be done simultaneously with
axial sectioning, in a technique called "non-null wavefront
compensation." The optical path for wavefront sensing is not
confocal, so light is detected from all scattered layers in the
retina simultaneously. Therefore, when the aberrations of the eye
are corrected, the defocus is also adjusted to put the focal plane
into the mean location of all the scattering layers in the retina.
If wavefront sensing and compensation were to be done
simultaneously with axial sectioning, the mirror would continually
try to adjust its defocus to move the image plane back to the mean
location of the scattering surfaces. Such a correction would defeat
attempts to change the focal plane of the system and image
different layers of the retina. This is overcome in the following
way. Rather than letting the AO system converge to a null state
(i.e., zero aberrations), the AO system is programmed to converge
to a finite defocused state. By converging to a defocused state,
the AO system will adjust the focal plane, while still correcting
all other aberrations to zero. This technique will allow the
operator to change the focal plane while still having the benefit
of simultaneous wavefront sensing and compensation.
The AOSLO described herein permits the direct imaging of features
in the living retina that have never been observed, features that
include retinal pigment epithelium cells, individual nerve fibers,
cone and rod photoreceptors, single capillaries in the retina and
choroid and white blood cells. With the improvements in axial
sectioning, it will be possible to generate the first microscopic
scale three-dimensional images of living human retina at high
resolutions.
The AOSLO can be used for the diagnosis of retinal disorders like
diabetic retinopathy, retinitis pigmentosa, age-related macular
degeneration, or glaucoma.
In still another use, high-resolution images of the retina will
permit highly accurate measurements of eye movements needed for
surgical applications or applications requiring eye tracking.
In yet another use, stimuli or treatment lasers are projected
directly onto the retina as part of the raster scan. Treatments
include photodynamic therapy, laser microphotocoagulation, and
microperimetry of the retina.
Images have been collected from the eyes of five persons ranging in
age from the 2.sup.nd to 7.sup.th decade. The RMS wavefront error
after AO compensation ranged from 0.05 to 0.15 .mu.m over a 6.3 mm
pupil. The patients used a dental impression mount fixed to an
X-Y-Z translation stage to set and maintain eye alignment during
the wavefront correction and imaging. The retinal location of the
wavefront correction and imaging was controlled by having each
patient view a fixation target. A drop of 1% tropicamide was
instilled to dilate the pupil and to minimize accommodation
fluctuations.
Experimental data will now be set forth. The correction of
aberrations provided by the present invention permits retinal
imaging of high quality, as will be seen.
FIGS. 6A and 6B show the same area of the retina of one patient
taken without (FIG. 6A) and with (FIG. 6B) aberration correction.
The RMS wavefront error was reduced from 0.55 to 0.15 .mu.m.
Another advantage was that correction of the aberrations caused
more light to be focused through the confocal pinhole, thus
increasing the amount of light for imaging. The inset in each of
FIGS. 6A and 6B shows a histogram of gray scales in the image.
FIGS. 7A-7C show axial sectioning of the retina, which is possible
because of the reduction in aberrations. The images are from a
location 4.5 degrees superior to the fovea. In FIG. 7A, the focal
plane is at the surface of the nerve fibers. FIG. 7B shows a
slightly deeper optical section in which less nerve fiber is seen
but the blood vessel is in focus. FIG. 7C shows an image in which
the focal plane is at the level of the photoreceptors, which are
about 300 .mu.m deeper than the image of FIG. 7A.
FIG. 8 shows a sequence of video frames in which the passage of a
white blood cell through the smallest retinal capillaries is
directly observed in a living human eye. The scale bar at the
bottom is 100 microns.
FIG. 9 shows images of cone photoreceptors resolved at retinal
locations from 0.5 to 4 degrees from the fovea. The long-dashed
line shows data from Curcio et al, "Human photoreceptor
topography," J. Comp. Neurol. 1990; 292:497-523, while the
short-dashed line shows psychophysical estimations of cone spacing
from D. Williams, "Topography of the foveal cone mosaic in the
living human eye," Vision Res. 28, 433-454 (1988).
Preliminary estimates of the resolution of the present invention
are about 2.5 .mu.m lateral and about 100 .mu.m axial. By contrast,
conventional SLO's have a typical resolution of 5 .mu.m lateral and
300 .mu.m axial.
The AOSLO of the preferred embodiment operates at a frame rate of
30 Hz, which permits visualization of blood flow in the retinal
capillaries. Also, the real-time imaging provides feedback on image
quality and image location. Further, axial sectioning can be
implemented. Conventional flood-illumination imaging, even with AO,
cannot offer such advantages.
The following article concerning the present invention is hereby
incorporated by reference in its entirety into the present
disclosure: A. Roorda et al, "Adaptive optics scanning laser
ophthalmoscopy," Optics Express, Vol. 10, No. 9, May 6, 2002, pp.
405-412.
While a preferred embodiment of the present invention and
variations thereon have been disclosed above, those skilled in the
art who have reviewed the present disclosure will readily
appreciate that other embodiments can be realized within the scope
of the invention. For example, numerical values are illustrative
rather than limiting. Also, variations on the configuration of the
common optical path are possible, and variations on the hardware
have been noted above. Further, while the present invention has
been disclosed with regard to human subjects, veterinary
applications are also possible. Therefore, the present invention
should be construed as limited only by the appended claims.
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